Infinity Has High Hopes for PI3K Inhibitor

Andrew D. Smith
Published: Thursday, Nov 07, 2013
Infinity PharmaceuticalsInfinity Pharmaceuticals of Cambridge, Massachusetts, began its efforts to produce innovative cancer treatments 12 years ago. Those efforts have put a number of experimental compounds to the test, but Infinity is still looking to bring its first novel agent to the market.

Less than 2 years ago, at the beginning of 2012, Infinity was running trials of three separate novel agents: the small-molecule Smoothened inhibitor saridegib (IPI-926), the heat shock protein 90 inhibitor retaspimycin HCl (IPI-504), and an oral PI3K inhibitor called IPI-145.

Today—following trial results that showed no survival benefits when either saridegib or retaspimycin HCl were paired with standard chemotherapy and tested against different tumors—Infinity has decided to focus its resources on PI3K inhibitors such as IPI-145, which continues to advance in clinical trials involving multiple conditions.

Infinity’s leadership has also changed over the years. The company was founded by Stephen Holtzman, a philosophy major who earned another philosophy degree as a Rhodes Scholar before becoming a pharmaceutical entrepreneur. Holtzman, in what Infinity described as an existing succession plan, surrendered executive control to current CEO Adele Q. Perkins in 2009, and surrendered his spot as chairman of Infinity’s board 2 years later, when he took an executive vice president job at another Bostonarea drugmaker, Biogen Idec.

Since Perkins began her tenure as Infinity’s CEO, the company has licensed IPI-145 from Intellikine, Inc, and tested the compound in both asthma and rheumatoid arthritis (RA), as well as several hematologic malignancies.

Infinity has reported positive phase I data for IPI-145 patients with B-cell lymphoma, chronic lymphocytic leukemia (CLL), and T-cell lymphoma.

In 51 patients with B-cell lymphoma, IPI-145 was found to be well tolerated and to produce responses in 68% of evaluable patients with indolent non-Hodgkin lymphoma and 67% of evaluable patients with mantle cell lymphoma. Patients who experienced responses tended to experience them early. Time to response ranged from 1.6 to 4.1 months, with a median time of 1.8 months.

In 34 patients with CLL, IPI-145 was again well tolerated. In terms of efficacy, 55% of 22 patients evaluable for response experienced partial responses, as defined by criteria from the International Workshop on Chronic Lymphocytic Leukemia. Stable disease was reported in nine patients, seven of whom had nodal responses.

In 17 patients with T-cell lymphoma, the most common grade ≥3 adverse event, ALT/AST elevation, occurred in 24% of patients. The response rate was 33%, including one complete response and one partial response in patients with peripheral T-cell lymphoma, and one partial response in a patient with cutaneous T-cell lymphoma. Stable disease was also reported in two other patients with cutaneous T-cell lymphoma.

Infinity is currently working on two trials in asthma and RA as well as three cancer trials:
  • A phase II study of IPI-145 in patients with refractory indolent non-Hodgkin lymphoma (NCT01882803)
  • A phase I study of IPI-145 in patients with advanced hematologic malignancies (NCT01476657)
  • A phase Ib study of IPI-145 in combination with bendamustine, rituximab or bendamustine/rituximab in hematologic malignancies (NCT01871675)


Infinity Pharmaceuticals Pipeline

Infinity Pharmaceuticals Pipeline

*25mg BID; †75 mg BID; NSCLC indicates non-small cell lung cancer.




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